AML及其WHO亚型与生活方式危险因素关系的病例对照研究
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摘要
目的分析BMI、吸烟、饮酒这3个主要生活方式危险因素对AML及其主要WHO亚型的风险的作用,以及其他环境暴露因子对这些作用的影响,为今后开展针对性预防和探索AML的机制提供依据。
对象与方法本研究采用1:2配对的病例对照研究设计。在2003年8月～2007年6月间,从29家协作医院选择所有成年上海籍AML新病例为病例组,同时,从同一家医院中按1:2个体配对的原则,选取2名沪籍、同性别、与病例年龄相差不超过5岁的其他良性病患作为对照。病例和对照的采集均遵循知情同意原则。采用统一设计的调查表,由经过培训的专职调查员以双盲的面对面问卷调查方式收集信息。调查内容包括人口学基本情况、家族史、既往疾病史、医疗史、职业史、生活方式暴露史和环境暴露史等。资料分析主要采用x~2检验、Mantel-Haenszel分层X~2检验和条件logsitic回归模型等统计方法。统计工具为SAS。
结果共收集到有效病例722名,其中AML-RCA 244名,AML-MD 186名,t-AML5名,AML-noc 269名;对照1444名,总有效应答率97.4%。控制混杂后,体重过轻、超重和肥胖的AML风险呈逐级下降趋势(OR和95%CI分别为1.00[0.72-1.38]、0.87[0.70-1.09]和0.67[0.46-0.97],P_(trend)=0.04)。男性在这3个BMI水平上发生AML的OR和95%CI分别为1.09(0.67-1.79)、0.93(0.69-1.25)和0.65(0.38-1.09),女性则分别为0.94(0.59-1.50)、1.04(0.72-1.49)和0.80(0.72-1.49),均未见显著等级趋势(P_(trend)均为0.31)。各亚型中,男性BMI与APL风险有正向趋势(P_(trend)=0.03),与AML-noc有负向趋势(P_(trend)=0.01)。装修过房屋的过瘦女性OR和95%CI为8.41和2.06-34.34。主动吸烟的AML风险高于参比(OR=1.28,95%CI=1.00-1.63),但吸烟量与AML风险无显著剂量反应趋势(P_(trend)=0.56)。在男性中少量吸烟、中度吸烟和大量吸烟发生AML的OR和95%CI分别为1.53(1.07-2.18)、1.26(0.87-1.82)和0.87(0.59-1.28),女性中则分别为0.63(0.25-1.62)、0.56(0.07-5.08)和1.20(0.19-7.40),均无剂量反应趋势(P_(trend)分别为0.98和0.82)。各亚型中,男性中度吸烟者AML-ETO的OR和95%CI为3.52(1.17-10.6),男性少量吸烟者AML-noc的OR和95%CI为2.40(1.22-4.71)。曾住在农村的少量吸烟的男性发生AML的OR和95%CI为2.21(1.06-4.61)。在3个吸烟量水平上,男性使用过中草药和不曾用过中草药发生AML的OR和95%CI依次分别为0.79(0.10-6.54)、1.45(1.03-2.05);0.64(0.08-5.28)、1.20(0.84-1.71);0.86(0.12-6.07)、0.87(0.60-1.27)。饮酒的AML风险高于参比(OR=1.53,95%CI=1.17-2.01),且饮酒量与AML风险有剂量反应趋势(P_(trend)=0.01)。在男性中少量饮酒与大量饮酒发生AML的OR和95%CI分别为1.35(0.92-1.97)和1.18(0.82-1.71),在女性中则分别为2.30(0.68-7.86)和1.50(0.21-10.9),均无剂量反应趋势(P_(trend)分别为0.16和0.23)。在2个饮酒量水平上,男性使用过中草药和不曾用过中草药发生AML的OR和95%CI依次分别为0.60(0.10-3.51)、1.37(0.94-2.07);(未获得估计)、1.25(0.87-1.80)。个别酒类中,饮用啤酒、米酒或黄酒、白酒发生AML的OR和95%CI分别为1.38(0.95-2.00)、1.47(1.03-2.09)和1.29(0.93-1.80)。这三种酒类的男性少量、大量饮用者发生AML的OR和95%CI依次分别为1.23(0.69-2.19)、1.12(0.69-1.84);0.95(0.52-1.73)、1.35(0.86-2.14);1.47(0.88-2.46)、0.85(0.54-1.34)。各亚型中,总饮酒量和啤酒饮用量与AML-noc风险有剂量反应趋势(P_(trend)分别为0.02和0.05),白酒男性少量饮用者发生AML-noc的OR和95%CI为3.84(1.29-11.5)。
结论AML的风险随着BMI增加而呈下降趋势,但在APL亚型中反之。吸烟可增加AML风险,且效应有亚型特异性。饮酒也增加AML风险,且有剂量反应趋势,但效应可能无亚型特异性。个别其他暴露特征对这3种生活方式的AML风险有增效作用,可针对这些亚组展开针对性预防。中草药可能对烟酒所增加的AML风险有一定保护作用。
A Hospital-basd Case-control Study on Lifestyle Risk Factors of Acute Myeloid Leukemia and Its WHO Subtypes
Objectives To analyse the effect of three major lifestyle risk factors(BMI,smoking and alcohol drinking) on AML(acute myeloid leukemia) and its WHO subtypes,as well as the impact of other environmental exposure upon this effect,both of which would facilitate the conduction of prevention for specific population at risk and the exploration of the disease mechanisms of AML.
Materials and methods A hospital-based,1:2 paired case-control study design is employed in this study.All AML patients,who were Shanghai residents,newly diagnosed during August 2003～June 2007 in the 29 participating hospitals were supposed to be selected as cases.By the meantime of the enrollment for each case,2 controls with the same gender,age difference no larger than 5 years,Shanghai residence and without malignant neoplasms or ever diagnosed with lympho-hematopoietic diseases were selected from the same hospistal.All participants were included after they had signed an informed consent designed according to Helsinki Declaration.A double-blinded face-to-faced interview with a 17-page carefully developed questionnaire was immediately conducted by trained interviewers.The questionnaire covers information on demographics,family history,disease history, medical history,occupational history,lifestyle exposure and environmental exposure. Chi-square test,Mantel-Haenszel stratified analysis and conditional as well as unconditional logsitic regression models were conducted using SAS for analysis.
Results A total of 722 effecient cases(among which 244 AML-RCA cases,186 AML-MD cases,5 t-AML cases and 269 AML-noc cases) and 1444 controls were included.Participation ratio reached 97.4%.Adjusted with recognized confoundings, compared with the BMI desirable group,the ORs and 95%CIs of underweight, overweight and obese upon AML-total were 1.00(0.72-1.38),0.87(0.70-1.09) and 0.67(0.46-0.97) respectively,with a negative trend among the risks(P_(trend)=0.04).For males,ORs and 95%CIs of the 3 BMI levels upon AML-total were 1.09(0.67-1.79), 0.93(0.69-1.25) and 0.65(0.38-1.09) respectively,while for females 0.94(0.59-1.50), 1.04(0.72-1.49) and 0.80(0.72-1.49) respectively.Significant trends were detected in neither of the genders(P_(trend)=0.31 both).There is a positive trend among BMI and APL risk in males(P_(trend)==0.03),but a negative trend among BMI and AML-noc (P_(trend)=0.01).Females with BMI＜18.5 who ever did house renovation have a significant elevated AML-total risk(OR=8.41,95%CI=2.06-34.34).Active smoking can elevate AML-total risk significantly(OR=1.28,95%CI=1.00-1.63),but without dose-response effect(P_(trend)=0.56).For males,ORs and 95%CIs of light,moderate and heavy smoking upon AML-total were 1.53(1.07-2.18),1.26(0.87-1.82) and 0.87(0.59-1.28) respectively,while for females 0.63(0.25-1.62),0.56(0.07-5.08) and 1.20(0.19-7.40) respectively.Significant dose-responese trends were detected in neither genders(P_(trend)=0.98 and 0.82 respectively).With regard to subtypes,male moderate smokers' AML-ETO risk was significantly elevated(OR=3.52. 95%CI=1.17-10.6).Male light smokers' AML-noc risk was also significantly elevated(OR=2.40,95%CI=1.22-4.71).Male light smokers who ever lived in a farm has a significantly elevated AML-total risk(OR=2.21,95%CI=1.06-4.61),which indicated a possible strengthened effect modification.Compared with male nonsmokers,male light,moderate and heavy smokers who ever used Chinese traditional medications had non-significantly reduced AML-total risks(OR=0.79, 95%CI=0.10-6.54;OR=0.64,95%CI=0.08-5.28;OR=0.86,95%CI=0.12-6.07),while smokers never used Chinses traditional medications had elevated AML-total risks (OR=1.45,95%CI=1.03-2.05;OR=1.20,95%CI=0.84-1.71;OR=0.87, 95%CI=0.60-1.27).Ever alcohol drinkers had an elevated AML-total risk(OR=1.53, 95%CI=1.17-2.01) and there was a positive dose-dependent trend among drinking dose and AML-total risk(P_(trend)=0.01).For males,light and heavy drinkers' ORs and 95%CIs were 1.35(0.92-1.97) and 1.18(0.82-1.71) respectively,while for females 2.30(0.68-7.86) and 1.50(0.21-10.9).Significant dose-dependent trends could be detected in neither genders(P_(trend)=0.16 and 0.23 respectively).Male light drinkers who ever used Chinese traditional medications had a non-significantly reduced AML-total risk(OR=0.60,95%CI=0.10-3.51),while male light and heavy drinkers who never used Chinese traditional medications had elevated AML-total risks (OR=1.37,95%CI=0.94-2.07;OR=1.25,95%CI=0.87-1.80 respectively).ORs and 95%CIs of beer,ricewine and hard liquor upon AML-total were 1.38(0.95-2.00), 1.47(1.03-2.09) and 1.29(0.93-1.80) respectively.ORs and 95%CIs of the three wine sub-categories for male light drinkers were 1.23(0.69-2.19),0.95(0.52-1.73) and 1.47(0.88-2.46),while for male heavy drinkers were 1.12(0.69-1.84),1.35(0.86-2.14) and 0.85(0.54-1.34) respectively.Regarding subtypes,total wine drinking and beer consumption had positive dose-dependent trends with AML-noc risk(P_(trend)=0.02 and 0.05 respectively).Male drinkers of hard liquor had a significantly elevated AML-noc risk(OR=3.84,95%CI=1.29-11.5).
Conclusion AML-total risk is reduced by increased BMI,but the subtype APL's risk is significantly elevated by increased BMI.Active smoking increases AML risk, which shows a certain WHO subtype-specificity.Alcohol drinking increased AML risk too,and shows a dose-dependent trend.But the effect may not be WHO subtpe specific.Some of the environmental exposure characteristics may have a strengthening modifying effect on the AML risk of the three lifestyles.We may recognize certain high risk sub-populations for specific preventions.The use of Chinses traditional medications shows a potential protective effect on AML risks of both tobacco smoking and alcohol drinking.
对象与方法本研究采用1:2配对的病例对照研究设计。在2003年8月～2007年6月间,从29家协作医院选择所有成年上海籍AML新病例为病例组,同时,从同一家医院中按1:2个体配对的原则,选取2名沪籍、同性别、与病例年龄相差不超过5岁的其他良性病患作为对照。病例和对照的采集均遵循知情同意原则。采用统一设计的调查表,由经过培训的专职调查员以双盲的面对面问卷调查方式收集信息。调查内容包括人口学基本情况、家族史、既往疾病史、医疗史、职业史、生活方式暴露史和环境暴露史等。资料分析主要采用x~2检验、Mantel-Haenszel分层X~2检验和条件logsitic回归模型等统计方法。统计工具为SAS。
结果共收集到有效病例722名,其中AML-RCA 244名,AML-MD 186名,t-AML5名,AML-noc 269名;对照1444名,总有效应答率97.4%。控制混杂后,体重过轻、超重和肥胖的AML风险呈逐级下降趋势(OR和95%CI分别为1.00[0.72-1.38]、0.87[0.70-1.09]和0.67[0.46-0.97],P_(trend)=0.04)。男性在这3个BMI水平上发生AML的OR和95%CI分别为1.09(0.67-1.79)、0.93(0.69-1.25)和0.65(0.38-1.09),女性则分别为0.94(0.59-1.50)、1.04(0.72-1.49)和0.80(0.72-1.49),均未见显著等级趋势(P_(trend)均为0.31)。各亚型中,男性BMI与APL风险有正向趋势(P_(trend)=0.03),与AML-noc有负向趋势(P_(trend)=0.01)。装修过房屋的过瘦女性OR和95%CI为8.41和2.06-34.34。主动吸烟的AML风险高于参比(OR=1.28,95%CI=1.00-1.63),但吸烟量与AML风险无显著剂量反应趋势(P_(trend)=0.56)。在男性中少量吸烟、中度吸烟和大量吸烟发生AML的OR和95%CI分别为1.53(1.07-2.18)、1.26(0.87-1.82)和0.87(0.59-1.28),女性中则分别为0.63(0.25-1.62)、0.56(0.07-5.08)和1.20(0.19-7.40),均无剂量反应趋势(P_(trend)分别为0.98和0.82)。各亚型中,男性中度吸烟者AML-ETO的OR和95%CI为3.52(1.17-10.6),男性少量吸烟者AML-noc的OR和95%CI为2.40(1.22-4.71)。曾住在农村的少量吸烟的男性发生AML的OR和95%CI为2.21(1.06-4.61)。在3个吸烟量水平上,男性使用过中草药和不曾用过中草药发生AML的OR和95%CI依次分别为0.79(0.10-6.54)、1.45(1.03-2.05);0.64(0.08-5.28)、1.20(0.84-1.71);0.86(0.12-6.07)、0.87(0.60-1.27)。饮酒的AML风险高于参比(OR=1.53,95%CI=1.17-2.01),且饮酒量与AML风险有剂量反应趋势(P_(trend)=0.01)。在男性中少量饮酒与大量饮酒发生AML的OR和95%CI分别为1.35(0.92-1.97)和1.18(0.82-1.71),在女性中则分别为2.30(0.68-7.86)和1.50(0.21-10.9),均无剂量反应趋势(P_(trend)分别为0.16和0.23)。在2个饮酒量水平上,男性使用过中草药和不曾用过中草药发生AML的OR和95%CI依次分别为0.60(0.10-3.51)、1.37(0.94-2.07);(未获得估计)、1.25(0.87-1.80)。个别酒类中,饮用啤酒、米酒或黄酒、白酒发生AML的OR和95%CI分别为1.38(0.95-2.00)、1.47(1.03-2.09)和1.29(0.93-1.80)。这三种酒类的男性少量、大量饮用者发生AML的OR和95%CI依次分别为1.23(0.69-2.19)、1.12(0.69-1.84);0.95(0.52-1.73)、1.35(0.86-2.14);1.47(0.88-2.46)、0.85(0.54-1.34)。各亚型中,总饮酒量和啤酒饮用量与AML-noc风险有剂量反应趋势(P_(trend)分别为0.02和0.05),白酒男性少量饮用者发生AML-noc的OR和95%CI为3.84(1.29-11.5)。
结论AML的风险随着BMI增加而呈下降趋势,但在APL亚型中反之。吸烟可增加AML风险,且效应有亚型特异性。饮酒也增加AML风险,且有剂量反应趋势,但效应可能无亚型特异性。个别其他暴露特征对这3种生活方式的AML风险有增效作用,可针对这些亚组展开针对性预防。中草药可能对烟酒所增加的AML风险有一定保护作用。
A Hospital-basd Case-control Study on Lifestyle Risk Factors of Acute Myeloid Leukemia and Its WHO Subtypes
Objectives To analyse the effect of three major lifestyle risk factors(BMI,smoking and alcohol drinking) on AML(acute myeloid leukemia) and its WHO subtypes,as well as the impact of other environmental exposure upon this effect,both of which would facilitate the conduction of prevention for specific population at risk and the exploration of the disease mechanisms of AML.
Materials and methods A hospital-based,1:2 paired case-control study design is employed in this study.All AML patients,who were Shanghai residents,newly diagnosed during August 2003～June 2007 in the 29 participating hospitals were supposed to be selected as cases.By the meantime of the enrollment for each case,2 controls with the same gender,age difference no larger than 5 years,Shanghai residence and without malignant neoplasms or ever diagnosed with lympho-hematopoietic diseases were selected from the same hospistal.All participants were included after they had signed an informed consent designed according to Helsinki Declaration.A double-blinded face-to-faced interview with a 17-page carefully developed questionnaire was immediately conducted by trained interviewers.The questionnaire covers information on demographics,family history,disease history, medical history,occupational history,lifestyle exposure and environmental exposure. Chi-square test,Mantel-Haenszel stratified analysis and conditional as well as unconditional logsitic regression models were conducted using SAS for analysis.
Results A total of 722 effecient cases(among which 244 AML-RCA cases,186 AML-MD cases,5 t-AML cases and 269 AML-noc cases) and 1444 controls were included.Participation ratio reached 97.4%.Adjusted with recognized confoundings, compared with the BMI desirable group,the ORs and 95%CIs of underweight, overweight and obese upon AML-total were 1.00(0.72-1.38),0.87(0.70-1.09) and 0.67(0.46-0.97) respectively,with a negative trend among the risks(P_(trend)=0.04).For males,ORs and 95%CIs of the 3 BMI levels upon AML-total were 1.09(0.67-1.79), 0.93(0.69-1.25) and 0.65(0.38-1.09) respectively,while for females 0.94(0.59-1.50), 1.04(0.72-1.49) and 0.80(0.72-1.49) respectively.Significant trends were detected in neither of the genders(P_(trend)=0.31 both).There is a positive trend among BMI and APL risk in males(P_(trend)==0.03),but a negative trend among BMI and AML-noc (P_(trend)=0.01).Females with BMI＜18.5 who ever did house renovation have a significant elevated AML-total risk(OR=8.41,95%CI=2.06-34.34).Active smoking can elevate AML-total risk significantly(OR=1.28,95%CI=1.00-1.63),but without dose-response effect(P_(trend)=0.56).For males,ORs and 95%CIs of light,moderate and heavy smoking upon AML-total were 1.53(1.07-2.18),1.26(0.87-1.82) and 0.87(0.59-1.28) respectively,while for females 0.63(0.25-1.62),0.56(0.07-5.08) and 1.20(0.19-7.40) respectively.Significant dose-responese trends were detected in neither genders(P_(trend)=0.98 and 0.82 respectively).With regard to subtypes,male moderate smokers' AML-ETO risk was significantly elevated(OR=3.52. 95%CI=1.17-10.6).Male light smokers' AML-noc risk was also significantly elevated(OR=2.40,95%CI=1.22-4.71).Male light smokers who ever lived in a farm has a significantly elevated AML-total risk(OR=2.21,95%CI=1.06-4.61),which indicated a possible strengthened effect modification.Compared with male nonsmokers,male light,moderate and heavy smokers who ever used Chinese traditional medications had non-significantly reduced AML-total risks(OR=0.79, 95%CI=0.10-6.54;OR=0.64,95%CI=0.08-5.28;OR=0.86,95%CI=0.12-6.07),while smokers never used Chinses traditional medications had elevated AML-total risks (OR=1.45,95%CI=1.03-2.05;OR=1.20,95%CI=0.84-1.71;OR=0.87, 95%CI=0.60-1.27).Ever alcohol drinkers had an elevated AML-total risk(OR=1.53, 95%CI=1.17-2.01) and there was a positive dose-dependent trend among drinking dose and AML-total risk(P_(trend)=0.01).For males,light and heavy drinkers' ORs and 95%CIs were 1.35(0.92-1.97) and 1.18(0.82-1.71) respectively,while for females 2.30(0.68-7.86) and 1.50(0.21-10.9).Significant dose-dependent trends could be detected in neither genders(P_(trend)=0.16 and 0.23 respectively).Male light drinkers who ever used Chinese traditional medications had a non-significantly reduced AML-total risk(OR=0.60,95%CI=0.10-3.51),while male light and heavy drinkers who never used Chinese traditional medications had elevated AML-total risks (OR=1.37,95%CI=0.94-2.07;OR=1.25,95%CI=0.87-1.80 respectively).ORs and 95%CIs of beer,ricewine and hard liquor upon AML-total were 1.38(0.95-2.00), 1.47(1.03-2.09) and 1.29(0.93-1.80) respectively.ORs and 95%CIs of the three wine sub-categories for male light drinkers were 1.23(0.69-2.19),0.95(0.52-1.73) and 1.47(0.88-2.46),while for male heavy drinkers were 1.12(0.69-1.84),1.35(0.86-2.14) and 0.85(0.54-1.34) respectively.Regarding subtypes,total wine drinking and beer consumption had positive dose-dependent trends with AML-noc risk(P_(trend)=0.02 and 0.05 respectively).Male drinkers of hard liquor had a significantly elevated AML-noc risk(OR=3.84,95%CI=1.29-11.5).
Conclusion AML-total risk is reduced by increased BMI,but the subtype APL's risk is significantly elevated by increased BMI.Active smoking increases AML risk, which shows a certain WHO subtype-specificity.Alcohol drinking increased AML risk too,and shows a dose-dependent trend.But the effect may not be WHO subtpe specific.Some of the environmental exposure characteristics may have a strengthening modifying effect on the AML risk of the three lifestyles.We may recognize certain high risk sub-populations for specific preventions.The use of Chinses traditional medications shows a potential protective effect on AML risks of both tobacco smoking and alcohol drinking.
引文
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